Malaria due to Plasmodium falciparum causes an estimated 564,000 deaths per year in sub-Saharan Africa. In Zambia, annual cases of malaria have increased every year since 2009, and malaria remains the single largest cause of child mortality. Malaria control is particularly challenging in the northern provinces, where parasite prevalence remains over 50% in children under 5 years, and resistance to pyrethroid and carbamate insecticides is widespread. Targeted household indoor residual spraying (IRS) is an emerging intervention strategy in low-resource settings that focuses on hotspots with high population density so resources can be concentrated on clusters of households that have the most impact in sustaining local transmission. As the global interest in targeted IRS increases, evaluations are needed to determine the effectiveness of this strategy in different settings. In addition, human population movement has been cited as an important driver of malaria transmission, but little is known about how movement affects individual malaria risk or how it might impact the effectiveness of a targeted intervention strategy. In the fall of 2014, a targeted IRS intervention was launched in Nchelenge District, Luapula Province, Zambia using a novel organophosphate insecticide pirimiphos-methyl, and this strategy is expected to be repeated in the fall of 2015. This research will contribute to better understanding the malaria transmission dynamics in a high burden setting in northern Zambia, and will provide a rigorous evaluation of this intervention strategy in the context of year-round malaria transmission, daily individual movement, and seasonal agricultural migration. Aim 1 will use serially collected cross-sectional household surveys from over 4.5 years of active surveillance to evaluate the impact of targeted IRS on malaria parasite prevalence in Nchelenge District. Both univariate methods and multivariate models will be used to determine the total, direct, and indirect effects of this intervention over multiple years. This will be the first study to assess the effectiveness of a targeted IRS strategy in a high transmission setting, and the first study to assess the effectiveness of pirimiphos-methyl in a high-transmission setting over multiple spray seasons. Aim 2 will evaluate the contribution of individual movement patterns to 30-day malaria risk using data from a year-long study implemented in 2014, in which 81 people carried a GPS data logger for one month, and incident malaria was identified. Descriptive statistics, multivariate models, and spatial statistics will be used to compare movement patterns of people who contracted malaria compared with those who did not. This research will be the first to describe individual movement patterns in a high malaria transmission setting and to explore these movement patterns as a risk factor for malaria incidence. This will also be among the first studies to evaluate the impact of individual human movement on the effectiveness of targeted interventions. The broad, long-term goals of this proposal are to guide malaria control strategies in rural sub-Saharan Africa.